Recapitulation of morphogenetic cell shape changes enables wound re-epithelialisation.

Recapitulation of morphogenetic cell shape changes enables wound re-epithelialisation.
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DOI:
10.1242/dev.107045
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发表时间:
2014-05
期刊:
Development (Cambridge, England)
影响因子:
--
通讯作者:
Martin P
Martin P
中科院分区:
其他
文献类型:
--
作者:
Razzell W;Wood W;Martin P

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创伤修复是维持组织稳态的基本保守机制,与胚胎形态发生有许多相似之处。简单上皮细胞中的小伤口在其前缘快速组装收缩性肌动球蛋白缆线,以及最终将伤口边缘编织在一起的动态丝状伪足。大多数关于伤口再上皮化的研究都集中在肌动蛋白机制上,这些机制聚集在前排细胞的前缘,并且类似于驱动形态发生事件的收缩机制,包括果蝇背侧闭合,但是,很明显,多个细胞排也必须有助于伤口的有效修复。在这里,我们研究了从伤口边缘回来的细胞的作用,并表明它们也向伤口伸展,伤口边缘前后的细胞重新排列它们与邻居的连接,以驱动细胞嵌入事件。在前后细胞中的这个过程是活跃的,并且依赖于导致连接的棘轮收缩的肌动球蛋白脉冲;肌动球蛋白脉冲的目标是在细胞顶点处的细胞极性蛋白Par 3中的断裂。抑制肌动球蛋白动力学从前缘返回防止连接收缩并抑制伤口边缘前进。这些事件概括了胚带延伸过程中发生的细胞重排,其中插入事件驱动组织的伸长。
Wound repair is a fundamental, conserved mechanism for maintaining tissue homeostasis and shares many parallels with embryonic morphogenesis. Small wounds in simple epithelia rapidly assemble a contractile actomyosin cable at their leading edge, as well as dynamic filopodia that finally knit the wound edges together. Most studies of wound re-epithelialisation have focused on the actin machineries that assemble in the leading edge of front row cells and that resemble the contractile mechanisms that drive morphogenetic episodes, including Drosophila dorsal closure, but, clearly, multiple cell rows back must also contribute for efficient repair of the wound. Here, we examine the role of cells back from the wound edge and show that they also stretch towards the wound and cells anterior-posterior to the wound edge rearrange their junctions with neighbours to drive cell intercalation events. This process in anterior-posterior cells is active and dependent on pulses of actomyosin that lead to ratcheted shrinkage of junctions; the actomyosin pulses are targeted to breaks in the cell polarity protein Par3 at cell vertices. Inhibiting actomyosin dynamics back from the leading edge prevents junction shrinkage and inhibits the wound edge from advancing. These events recapitulate cell rearrangements that occur during germband extension, in which intercalation events drive the elongation of tissues.
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